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Frontotemporal Dementia and Frontotemporal Lobar Degeneration

Overview

The presentation of degenerative disease in focal areas of the cerebral cortex is the hallmark of the family of diseases referred to as frontotemporal dementia (also termed frontotemporal lobar degeneration). Cases of elderly patients with progressive language deterioration have been described since Arnold Pick’s landmark case report of 1892. His case study “On the relationship between aphasia and senile atrophy of the brain “still serves as a frame of reference for apparently focal brain syndromes in diffuse or generalized degenerative diseases of the brain.
As Pick stated, “simple progressive brain atrophy can lead to symptoms of local disturbance through local accentuation of the diffuse process.”

In the 1980s and 1990s, 2 parallel streams of information accumulated related to focal brain degenerations. In 1982, Mesulam reported 6 patients with progressive aphasia, gradually worsening over a number of years, who did not develop a more generalized dementia.
Since Mesulam’s publication, numerous other cases have been reported, and Mesulam’s group has contributed additional reviews.
This disorder, which is currently termed primary progressive aphasia (PPA), has gained acceptance as a syndrome.

Subsequently, the PPA syndrome was defined as a disorder limited to progressive aphasia, without general cognitive impairment or dementia, over a 2-year period.
Many patients develop more generalized dementia later in the course of the illness, as reported by Kirshner et al.
Less commonly, cases of isolated right frontal or temporal degeneration have been reported.
These patients experience failure to recognize family members (prosopagnosia), failure to remember topographic relationships, and similar disorders. (See the image below.)

Hematoxylin and eosin stain of the left frontal co

Hematoxylin and eosin stain of the left frontal cortex from a patient with primary progressive aphasia. This shows loss of neurons, plump astrocytes (arrow), and microvacuolation of the superficial cortical layers. Reproduced with permission of John Wiley & Sons, Inc.

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In England and Europe, cases of frontal lobe dementia were described with progressive dysfunction of the frontal lobes. In a series of case reports, Neary and Snowden outlined a syndrome with initial symptoms that were suggestive of psychiatric illness. However, the following frontal lobe behavioral abnormalities appeared over time:

Disinhibition

Impulsivity

Impersistence

Inertia

Loss of social awareness

Neglect of personal hygiene

Mental rigidity, stereotyped behavior

Utilization behavior – Ie, a tendency to pick up and manipulate any object in the environment

These descriptions included language abnormalities such as reduced speech output, mutism, echolalia, and perseveration.

The condition described in the North American literature as primary progressive aphasia and that described in the European literature as frontal dementia have been combined under the term frontotemporal lobe dementia (FTD), or frontotemporal lobar degeneration (FTLD). Within this grouping, the frontal lobe syndrome described by Neary and Snowdon,
is referred to as, interchangeably, behavioral variant frontotemporal lobe dementia (bvFTD) or frontal variant frontotemporal lobe dementia (fvFTD). The progressive aphasias have been divided into 3 groups: progressive nonfluent aphasia, semantic dementia, and logopenic progressive aphasia.

In recent years, the term frontotemporal dementia has become an umbrella term referring to clinical syndromes of frontal dementia or progressive aphasia. An alternate term, frontotemporal lobar degeneration, relates to pathologies associated with the frontotemporal lobe dementia syndromes. In this review, the 2 terms are used more or less synonymously.

Treatment

To date, most efforts have concentrated on diagnosing FTD and understanding its pathogenesis. Once the abnormal gene products are better understood, specific medical treatments may emerge. At present, however, medical treatment is extremely limited.

Social interventions, counseling, and speech/language/cognitive therapy to facilitate the use of spared functions may make the condition easier to bear for the patient, caregivers, and family members. Whether behavioral interventions slow the progression of the disease remains to be proved.

All current pharmacologic treatments are unproved, but selective serotonin reuptake inhibitor (SSRI) antidepressants and trazodone are widely recommended.
Cholinesterase inhibitors, approved for Alzheimer disease, are sometimes used in this condition, but there is no evidence that FTD involves a cholinergic deficit, and there is no clinical evidence of benefit.
Anecdotally, some patients may improve in terms of memory, but others seem to worsen in behavior. Likewise, the drug memantine (Namenda) has been used in FTD, but 2 recent small clinical trials failed to confirm any benefit.
It is hoped that future breakthroughs in the molecular biology and genetics of these disorders may lead to disease-modifying treatments.

Patient education

For patient education information, see the Brain and Nervous System Center, as well as Dementia Overview and Dementia Medication Overview.

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